QuestionWhat is the optimal concentration of topical sirolimus for the treatment of facial angiofibromas in tuberous sclerosis complex?

FindingsIn this randomized clinical trial of 18 children and 18 adults, sirolimus gel at a concentration of 0.2% demonstrated significantly more improvement at the end of treatment compared with placebo, with minimum toxic effects.

MeaningTopical treatment with a 0.2% concentration of sirolimus gel will be a useful medication for facial angiofibromas in tuberous sclerosis complex.

ObjectiveTo evaluate the efficacy, safety, and optimal concentration of a topical sirolimus gel vs placebo for treatment of facial angiofibromas in TSC.

Design, Setting, and ParticipantsA double-blind, placebo-controlled, parallel-group, dose-escalation, phase 2 randomized clinical trial using 3 sirolimus gel concentrations was performed at Osaka University Hospital, Osaka, Japan. Thirty-six patients with TSC and facial angiofibromas, including 18 aged 3 to 18 years (children) and 18 aged 19 to 65 years (adults), were enrolled from December 10, 2013, to July 17, 2014. Analysis was by intention to treat.

InterventionsThe adult and child groups were each subdivided into 3 groups (n = 12 each) and randomized to receive sirolimus gel concentrations of 0.05%, 0.1%, or 0.2% or placebo using a web-response system in a 2:1 fashion. The medication was applied to the patient’s lesions twice per day for 12 weeks. Each patient underwent assessment at 2, 4, 8, and 12 weeks during treatment and at 4 weeks after discontinuation of the treatment (16 weeks).

Main Outcomes and MeasuresThe primary end point, planned before starting data collection, was an improvement factor, represented as a variable composed of tumor size reduction and a lessening of the redness of the 3 target tumors at 12 weeks relative to baseline.